Submissions for variant NM_001378454.1(ALMS1):c.8221C>T (p.Gln2741Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002510385	SCV002819628	pathogenic	Alstrom syndrome	2022-12-02	criteria provided, single submitter	clinical testing	Variant summary: ALMS1 c.8218C>T/p.Gln2740X (also known as c.8224C>T/p.Gln2742X in RefSeq) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 249458 control chromosomes. c.8218C>T has been reported in the literature in individuals affected with Alstrom Syndrome. These data indicate that the variant is likely to be associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002510385	SCV004292595	pathogenic	Alstrom syndrome	2023-03-11	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1878332). This variant is also known as Q2471X. This premature translational stop signal has been observed in individual(s) with Alström syndrome (PMID: 18654604, 21157496). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln2742*) in the ALMS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715).